SummaryClonidine has proved to be a clinically useful adjunct in clinical anaesthetic practice as well as in chronic pain therapy because it has both anaesthetic and analgesic-sparing activity. The more selective alpha-2 adrenoceptor agonists, dexmedetomidine and mivazerol, may also have a role in providing haemodynamic stability in patients who are at risk of peri-operative ischaemia. The side-effects of hypotension and bradycardia have limited the routine use of alpha-2 adrenoceptor agonists. Investigations into the molecular pharmacology of alpha-2 adrenoceptors have elucidated their role in the control of wakefulness, blood pressure and antinociception. We discuss the pharmacology of alpha-2 adrenoceptors and their therapeutic role in this review.

Dexmedetomidine is a highly selective alpha 2-adrenoceptor agonist with anaesthetic-sparing effects. We have determined the pharmacodynamic and pharmacokinetic interactions between dexmedetomidine and isoflurane in volunteers. Nine male subjects were allocated randomly to receive isoflurane anaesthesia preceded by infusion of dexmedetomidine on three separate occasions, 2 weeks apart. Dexmedetomidine target plasma concentrations were 0.0 (placebo), 0.3 ng ml-1 (low-dex) and 0.6 ng ml-1 (high-dex). End-tidal isoflurane concentrations at which gross purposeful movement and response to verbal commands occurred were identified. In the recovery period, sedation scores and digit symbol substitution tests were recorded. Venous blood samples were obtained before, during and after anaesthesia at predetermined intervals for measurement of plasma concentrations of dexmedetomidine and calculation of standard pharmacokinetic indices (AUC, Cl, Vss, T1/2 alpha, T1/2 beta). The end-tidal isoflurane concentration at which 50% of subjects first responded to the tetanic stimulus was 1.05% in the placebo group, 0.72% in the low-dex group and 0.52% in the high-dex group. We conclude that dexmedetomidine decreased isoflurane requirements in a dose-dependent manner and reduced heart rate, systolic and diastolic arterial pressures. Sedation and slight impairment of cognitive function persisted for several hours after anaesthesia and the end of infusion of dexmedetomidine. Isoflurane did not appear to influence the pharmacokinetics of dexmedetomidine.

We have studied the effects of whole body cooling on phrenic nerve and diaphragmatic function in 26 patients using magnetic stimulation of the phrenic nerves with a pair of Magstim 200 HP stimulator coils during cardiopulmonary bypass. The diaphragmatic electromyogram in response to magnetic pulses was recorded with needle electrodes at two temperatures, approximately 31 degrees C (cold) and approximately 36 degrees C (warm) during the cooling or rewarming phase of hypothermic cardiopulmonary bypass. This 5 degrees C temperature change was associated with clear changes in the evoked electromyographical response of the diaphragm. Median latency between stimulus and electromyographic response was 10.1 (range 8.0-11.8) ms during cold and 8.3 (5.9-10.2) ms during warm stimulation (P < 0.001). Median duration of the muscle compound action potential was prolonged and its amplitude reduced in cold compared with warm stimulations (P < 0.01). These effects were enhanced by application of ice slush to the heart. We conclude that diaphragmatic function may be affected by mild hypothermia after cardiac surgery.

SummaryWe investigated a total of 36 subjects with a mean (SD) age of 65 (13) years, during baseline conditions (supine, before any anaesthesia), and then during one of the following protocols: (1) lithotomy positioning (n ¼ 12), (2) epidural anaesthesia (n ¼ 12), (3) general anaesthesia in the supine position (n ¼ 12). Lung aeration, ventilation/perfusion matching, gas exchange and functional residual capacity were measured. Lung aeration was normal during baseline assessment with almost no regions with poor aeration and no substantial dependent densities. Shunt and perfusion of poorly ventilated regions were minor. Lithotomy positioning did not reduce functional residual capacity and did not affect aeration of the lung or ventilation/perfusion matching. Epidural anaesthesia, in general, had no effect on aeration, ventilation/perfusion matching or gas exchange, regardless of whether the patient was in the supine or lithotomy position. General anaesthesia, however, caused significant increases in poorly aerated lung regions and in dependent densities (interpreted as atelectasis). In conclusion, no or little impairment of lung aeration and ventilation/perfusion matching was caused by the lithotomy position and/or epidural anaesthesia, contrary to the effects seen during general anaesthesia. However, our findings also suggest that being overweight is a factor that may cause impairment of lung aeration.

Endovascular treatment of mesenteric ischemia is a safe and effective therapy with acceptable long-term results. Our experience with acute mesenteric ischemia suggests that percutaneous treatment may be an effective alternative to surgical revascularization in appropriately selected patients.